Cartridge For A Biological Sample

ABSTRACT

A sealed removable cartridge adapted for insertion into an assay device and adapted to contain a biologic sample, the cartridge comprising: two or more assay locations adapted to facilitate, within said cartridge, two or more assays of said biologic sample; and an actuator interface adapted to interface with an actuator of said assay device, to transport said biologic sample towards at least one of said assay locations.

FIELD OF THE DISCLOSURE

Embodiments of the disclosure relate to a cartridge for a biologicsample.

BACKGROUND

When diagnosing a sample, it is often required to reach a significantconclusion with respect to the sample's contents. Biological samples,such as semen, vaginal secretions, vaginal cells, blood, urine, saliva,lymph and the like, are commonly tested at the field, with portableapparatuses, tools or disposable diagnostics, or in laboratories.Laboratory work, including field work, often requires taking a portionof the sample, processing it in various ways using laboratory operationsand finally assessing a result. Laboratory medicine commonly includesanatomic pathology histopathology, cytopathology, microscopy, clinicalmicrobiology, bacteriology, virology, parasitology, immunology,mycology, clinical biochemistry instrumental analysis, enzymology,toxicology, endocrinology and hematology.

Over the past years, automated analyzers became more and more common inlaboratories. An automated analyzer is often defined as a medicallaboratory instrument designed to rapidly measure different chemicalsand other characteristics in a samples, with minimal human assistance.The automation of laboratory testing does not usually remove the needfor human expertise (as some results must still be evaluated by medicaltechnologists and other qualified clinical laboratory professionals, andsometimes manual processing is required), but it does ease concernsabout error reduction, staffing concerns and safety.

Applicant's U.S. Provisional Patent Application No. 60/981,856, filedOct. 23, 2007, discloses a diagnostic device. This application isincorporated herein by reference in its entirety.

SUMMARY

There is provided, according to an embodiment, a sealed removablecartridge adapted for insertion into an assay device and adapted tocontain a biologic sample, the cartridge comprising: two or more assaylocations adapted to facilitate, within said cartridge, two or moreassays of said biologic sample; and an actuator interface adapted tointerface with an actuator of said assay device, to transport saidbiologic sample towards at least one of said assay locations.

In some embodiments, said biologic sample is selected from a group whichincludes: a semen sample, a vaginal secretion sample, a vaginal cellsample, a blood sample, a urine sample, a saliva sample, a lymph sampleand/or any combination thereof.

In some embodiments, said two or more assays are selected from a groupwhich includes: a sperm concentration assay, a semen pH assay, aleukocyte threshold assay, a sperm motility assay, a sperm morphologyassay, a semen volume assay, a viscosity assay, a turbidity assay,and/or any combination thereof.

In some embodiments, said at least one of said assays is adapted tofacilitate diagnosis of at least one sexually transmitted disease (STD)selected from a group which includes: syphilis, gonorrhea, candida,human papiloma virus (HPV), mycoplasma, ureaplasma, humanimmunodeficiency virus (HIV), Chlamydia, herpes simplex virus, HepatitisB, Trichomonas, Hepatitis C and/or any combination thereof.

In some embodiments, a housing of said cartridge is substantially rigid.

In some embodiments, a housing of said cartridge is substantiallyflexible.

In some embodiments, said cartridge further comprises a cell separationsystem, comprising: a first chamber adapted to contain at least aportion of said semen sample; and a second chamber adapted to receivemotile cells upon introduction of a separation-enabling agent into saidfirst chamber.

In some embodiments, said cell separation system is adapted to assessmotility of sperm cells.

In some embodiments, said cell separation system is adapted to isolatemotile sperm of said semen sample for a usage selected from a groupconsisting of: intra uterine insemination (IUI), vaginal insemination,and in-vitro fertilization (IVF).

In some embodiments, the cartridge is further adapted to manipulate saidbiologic sample using at least one manipulation technique selected froma group which includes: homogenization, liquefaction, deposition on areagent-loaded pad, mixing with a reagent, deposition on anantibody-loaded pad, incubation, separation, migration, sedimentationand/or any combination thereof

There is further provided, according an embodiment, a method for using asealed removable cartridge for performing two or more assays, the methodcomprising: inserting the cartridge into a compartment of an assaydevice; inserting a biologic sample into the cartridge; and activatingthe assay device to facilitate, within the cartridge, two or more assaysof the biologic sample.

In some embodiments, the method further comprises operating an actuatorof the assay device for interfacing with the cartridge and fortransporting the biologic sample towards at least two assay locationswhere the two or more assays are facilitated.

In some embodiments, the biologic sample is selected from a group whichincludes: a semen sample, a vaginal secretion sample, a vaginal cellsample, a blood sample, a urine sample, a saliva sample, a lymph sampleand/or any combination thereof.

In some embodiments, the two or more assays are selected from a groupwhich includes: a sperm concentration assay, a semen pH assay, aleukocyte threshold assay, a sperm motility assay, a sperm morphologyassay, a semen volume assay and/or any combination thereof

In some embodiments, at least one of the assays is adapted to facilitatediagnosis of at least one STD selected from a group which includes:syphilis, gonorrhea, candida, HPV, mycoplasma, ureaplasma, HIV,Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis Cand/or any combination thereof.

In some embodiments, the method further comprises operating acomputerized control of the assay device for performing at least oneaction selected from a group which includes: facilitate at least one ofthe assays, receive a reading from said at least one sensor of the assaydevice, compute a result of at least one of the assays, compute acombined measure of results of two or more of the assays, compute apredicted optimal fertilization date and/or any combination thereof.

In some embodiments, the method further comprises operating a cellseparation system of the cartridge, the operating comprising: depositingat least a portion of the semen sample in a first chamber of the cellseparation system; introducing a separation-enabling agent into thefirst chamber, to facilitate swimming of motile cell into a secondchamber of the cell separation system.

In some embodiments, the method further comprises collecting the motilecells from the second chamber.

In some embodiments, the collecting of the motile cells comprisescollecting of motile sperm, for a usage selected from a group whichincludes: IUI, vaginal insemination, IVF and/or any combination thereof.

In some embodiments, the method further comprises assessing motility ofcells based on a relative amount of motile cells in the second chamber.

There is further provided, according to an embodiment, a cell separationsystem, comprising: a first chamber adapted to contain at least aportion of said semen sample; and a second chamber adapted to receivemotile cells upon introduction of a separation-enabling agent into saidfirst chamber.

In some embodiments, the system is further adapted to assess motility ofsperm cells.

In some embodiments, the system is further adapted to isolate motilesperm of said semen sample for a usage selected from a group whichincludes: intra uterine insemination (IUI), vaginal insemination,in-vitro fertilization (IVF) and/or any combination thereof.

In some embodiments, the system is enclosed within a sealed cartridgeadapted for insertion into an assay device.

There is further provided, according to an embodiment, a method foroperating a cell separation system, the method comprising: depositing atleast a portion of the semen sample in a first chamber of the cellseparation system; introducing a separation-enabling agent into thefirst chamber, to facilitate swimming of motile cells into a secondchamber of the cell separation system.

In some embodiments, the method further comprises collecting the motilecells from the second chamber.

In some embodiments, the collecting of the motile cells comprisescollecting of motile sperm, for a usage selected from a group consistingof: IUI, vaginal insemination, and IVF.

In some embodiments, the method further comprises assessing motility ofcells based on a relative amount of motile cells in the second chamber.

In addition to the exemplary aspects and embodiments described above,further aspects and embodiments will become apparent by reference to thefigures and by study of the following detailed description.

BRIEF DESCRIPTION OF THE FIGURES

Exemplary embodiments are illustrated in referenced figures. Dimensionsof components and features shown in the figures are generally chosen forconvenience and clarity of presentation and are not necessarily shown toscale. It is intended that the embodiments and figures disclosed hereinare to be considered illustrative rather than restrictive. The figuresare listed below.

FIG. 1A shows an exploded view of a sealed, removable cartridge;

FIG. 1B shows a perspective view of a main body of a sealed, removablecartridge;

FIG. 1C shows a perspective view of another sealed, removable cartridge;

FIG. 2 shows an exploded view of an assay device;

FIG. 3A shows a cross-sectional view of a cell separation system;

FIG. 3B shows a top view of a cell separation system;

FIG. 4A shows a perspective view of an assay device;

FIG. 4B shows a perspective view of a receptacle; and

FIG. 4C shows a cross-sectional view of an assay device.

DETAILED DESCRIPTION

An aspect of some embodiments related to an assay device adapted toreceive a sealed, removable cartridge containing a biologic sample. Theassay device, in conjunction with the cartridge, may be used forassessing, by way of at least one assay, one or more parameterspertaining to the biologic sample. Additionally or alternatively, theassay device may be used for treating the biologic sample, such as, inthe case of a semen sample, preparing it for intra uterine insemination(IUI), vaginal insemination, and/or in-vitro fertilization (IVF).

The biologic sample may be, for example, a semen sample, a vaginalsecretion sample, a biologic cell sample, cervical mucus, a bloodsample, a urine sample, a saliva sample, a lymph sample, or any othersample of biologic matter collected from a human or any other animal.

The cartridge may be substantially sealed, so that its biologic contentsdo not come in direct contact with the assay device and therefore nosubstantial contamination of the assay device and/or its immediatesurroundings is caused. The sealed cartridge may, however, include aninput port through which the biologic sample is fed, and/or an exhaustfor discarding excess pressure—but both features may be configured insuch a way that no substantial contamination is caused

The assay device may interface with the cartridge using an actuatoradapted to transport the biologic sample within the cartridge, towardsone or more locations within the cartridge referred to as assay port(s)and/or treatment port(s), where the biologic sample is assessed and/ortreated, respectively.

After use, the cartridge may be removed from the assay device anddiscarded. Alternatively, the cartridge may be stored (such as in cooledor cryogenic storage), along with its contents, for future testing,analysis and/or treatment of the sample. The cartridge may be configuredsuch that only a part of it, containing portion of sample or the treatedsample, is removed and stored for further testing, analysis and/ortreatment.

The assay device may be relatively easy to operate and its operation mayrequire no special laboratory training, so that a nurse, a physician, orany other caregiver may operates it in what is often referred to as a“point of care—a clinic, a medical institution or the like. Furthermore,the assay device may still be operated at the field, such as withportable apparatuses, tools or disposable diagnostics or in alaboratory.

Another aspect of some embodiments relates to an assay device adapted toreceive a receptacle, such as a condom or any sample collection cup,containing a reproductive system sample such as semen, a vaginalsecretion, any type of cell found in the vagina, cervical mucus and/orthe like. In case the sample is semen, the assay device may be used forassessing, using at least one assay, one or more parameters pertainingto the semen sample and/or for treating the sperm sample.

The assay device may include an extraction mechanism for extracting thesemen sample from the receptacle and for transporting the semen sampletowards one or more assay locations where the semen sample is assessed.

The assay device may further include a result indicator, such as acolor-changeable pad, for conveying the assessment results to its user.

Optionally, the user is the reproductive system sample provider, and,accordingly, the assay device may be adapted for use by a non-medicallytrained person. The assay device may be therefore offered to consumerseither as a prescription medical device or as an over-the-counter (OTC)non-prescription device.

An additional aspect of some embodiments relates to the sealed,removable cartridge itself, which may be adapted for use in conjunctionwith an assay device or as a standalone solution.

The cartridge may be essentially rigid or essentially flexible, and mayinclude an actuator interface for interfacing with an external means ofpressure creation, so as to transport the biologic sample towards one ormore assay and/or treatment ports. In case the cartridge is used withthe assay device, the means of pressure difference creation may be apart of the assay device. Additionally or alternatively, the actuatormay be an essentially flexible area of the cartridge, which may bepressed, optionally manually, to transport the sample.

A further aspect of some embodiments relates to a cell separationsystem. When used with sperm cells, it is adapted to assess motility ofsperm cells and/or to isolate motile sperm cells of the semen sample forintra uterine insemination (IUI), vaginal insemination, or in-vitrofertilization (IVF) purposes. The cell separation system may also beused for separating other types of motile cells from immotile cells.

The cell separation system may include a first chamber adapted tocontain at least a portion of a semen sample, and a second chamberadapted to receive motile cells upon introduction of aseparation-enabling agent into the first chamber. Theseparation-enabling agent may be a gas, a liquid, a gel and/or any othersuitable substance. After the separation, the first chamber may includean enriched population of immotile cells while the second chamber mayinclude an enriched population of motile cells.

The cell separation system is optionally enclosed within the cartridgewhich is, in turn, adapted for insertion into the assay device.Alternatively, the cell separation system may be used as a standalonedevice, separate from the cartridge and assay device discussed above.

A Cartridge

Reference is now made to FIG. 1A, which shows an exploded view of anexemplary sealed, removable cartridge 100 (hereinafter “cartridge”), inaccordance with an embodiment. Cartridge 100 may include a main body102, a top cover 104 and optionally a base 106. Main body 102 is alsoshown, from a perspective view, in FIG. 1B. Main body 102 may be shapedas a rectangular box, a cylinder a flexible pouch and/or the like.

At least one of main body 102, top cover 104 and base 106 (the at leastone of them may be jointly referred to as a “housing”) may beessentially rigid, optionally made of a rigid material such as apolymer, a metal, glass or the like; alternatively, the at least one ofmain body 102, top cover 104 and/or base 106 may be made of acombination of rigid materials or of a combination of at least one rigidmaterial and at least one flexible material.

Main body 102 may include an inlet 108 a for insertion of a biologicsample into cartridge 100. A matching hole 108 b may exist in top cover104, to allow for a connection of a sample cup (not shown) to cartridge100. The sample cup may have a tip adapted to be inserted, at leastpartially, into hole 108 b and into inlet 108 a, for supplying thebiologic sample, while maintaining overall sealing as discussed above.

The inserted biologic sample may be transported inside cartridge 100 byvirtue of at least one vacuum conduit, such as conduits 110. Conduits110 may include internal tubing not visible in this figure. Conduits110, when containing fluid, may be in contact with at least one actuatorinterface, such as actuator interfaces 112 a-b. Actuator interfaces 112a-b may be shaped as a niche (optionally arched) in main body 102.

At least one external actuator (not shown) interfacing with actuatorinterfaces 112 a-b, may provide conduits 110 with positive or negativegas pressure, so that the biologic sample is pushed or pulled along theconduits. For example, the actuator may be a peristaltic pump adapted toapply peristaltic pressure on a flexible pipe 114 which is in fluidcontact with conduits 110. Flexible pipe 114 may be secured in placeusing, for example, two holders 116. Since there is optionally no fluidcontact with the outside environment, by virtue of the peristaltic pumpwhich operates externally on flexible pipe 114, the interfacing with theactuator does not cause contamination of the environment outsidecartridge 100. For this purpose, any positive displacement system suchas a syringe or a micropipette may be used. In some cases,electromagnetic fields may induce transportation of the sample or partof the sample using, for example, electrophoresis. In some cases, anelectron enriched material such as a salt gradient may be used.

Alternatively or additionally, another actuator interface (not shown)may be an essentially flexible portion of cartridge 100 and/or itsinternal tubes, adapted for manual squeezing in order to transport thebiologic sample.

A set of filters 118 may be positioned in between the edge of conduits110 and an elevation 120 of base 106. Similarly, a filter 122 may bepositioned in between a volume compartment 124 and another elevation 126of base 106. Filters 122 and 118 may, by virtue of a suitably small poresize, provide ventilation to cartridge 100, while preventing leakage ofhazardous materials to the environment.

Cartridge 100 may include two or more assay locations adapted tofacilitate, within the cartridge, two or more assays of the biologicsample. The term “assay location”, as referred to herein, may refer toany site within cartridge 100 adapted to act on the biologic sampleand/or to analyze (or enable analysis by an external sensor of an assaydevice) at least one parameter pertaining to the sample.

For example, optionally when the sample is semen, the two or more assaylocations may be selected from the following: at least one result padsuch as two result pads 128; at least one pH and/or leukocytes test 132;at least one morphology assay 134; at least one reagent location, suchas five reagent locations 136; at least one homogenizer, such as twohomogenizers 138; at least one cell separation system 140; and at leastone free volume compartment 124.

The assay location may be adapted to perform assays such as: Acrosomreaction assay, with or without calcium ionophore; a 23187 ARIC test andprogesterone; bio active recombinant human ZP3 or active synthetic ZP3peptides or analogues; adding reagent (for example7-amino-actinomycin-D) to identify necrotic cells (SYTO 16) and readingresults at 610 nm to 670 nm hence detecting apoptosis; Sangersequencing; microplate assay; Polymerase Chain Reaction (PCR);probe-based hybridization assay; Processor Aided Motility count (CASA);Peroxidase; Zinc at 560 nm; Fructose at 470 nm; glucosidase at 405 nm;heavy metals assay; hormones such as Progesterone, Testosterone, andEstrogen; Antigen and/or cancer markers such as PSA, trace elements,carbohydrates proteoglycans or glycoproteins, minerals blood cells,plasma sexually transmitted disease (STD) assay (such as bacteria;yeast; Candida; virus) germs; Hidukes; Cervix carcinoma assay; PAPsmear, blood assay; saliva assay; urine stick assay; Immunobead assay;mixed antiglobuline reaction test (MAR test) assay; induced acrosomreaction assay; measurement of reacting oxygen assay; ROS—Oxidativestress, anti oxidants, sperm-cervical mucus interaction assay,turbidity, viscosity and/or the like in ways known in the prior art.

The assay location may perform its assay at least partially bymanipulating the biologic sample. By way of example, the assay locationmay utilize one or more of the following sample manipulation techniques:homogenization, liquefaction, mixing with a reagent, mixing with anantibody, deposition on a reagent-loaded pad, deposition on anantibody-loaded pad, concentration assessment, incubation, separation,migration, sedimentation viscosity assessment, turbidity, and the like.

The assay may be adapted to facilitate diagnosis of at least one STD.For example, syphilis, gonorrhea, candida, human papiloma virus (HPV),mycoplasma, ureaplasma, human immunodeficiency virus (HIV), Chlamydia,herpes simplex virus, Hepatitis B, Trichomonas, Hepatitis C and/or anyother STD or infection.

The assay may further be adapted to facilitate diagnosis of one or morefertility factors or indicators of the tested subject, such as spermcell concentration, semen volume, sperm cell morphology, semen pH,female secretion, sperm-cervical mucus interaction and/or the like

Result pads 128 may be loaded with a reagent, and when sample isdelivered via tips 130, reaction occurs and a result is shown (alsoreferred to as classical flow-through diagnostics). Result pad 128 maybe used as a strainer of the sample if reaction with reagents isperformed within the homogenizer, as described below. Result pad 128 maybe coupled with an antibody agent. When the sample is delivered via tips130, it flows on or within result pads 128 until in reaction with anantibody compound (also referred to as classical lateral flowdiagnostics). For example, anti CD 59 Result pad 128 may be operable foradding a reagent to the sample already on the result pad, using a gasand/or a liquid. The gas and/or the liquid may flow onto the samplethrough tips 130. Results may be read visually as color, a texture, ashape and/or the like. Results may also be read by a sensor.

Homogenizers 138 may be operable for homogenizing the sample prior toperforming further assays and/or for mixing the sample with otherreagents and/or biological components. Homogenization may be achievedvia rapid movement of the sample, such as by mixing it using arotateable or a reciprocating member. For example, triangular mixers 138a may be used for mixing the sample.

Semen pH threshold and leukocytes threshold tests 132 may include anabsorbent pad holder 132 a. The pad may include a color-changeablereagent indicating pH level, and/or a color-changeable reagentindicating leukocyte level. Such pads are available from differentmanufacturers.

Sperm cell morphology assay 134, which is shown only schematically sinceit is located within main body 102, may be adapted to hold, mark, stainand/or analyze morphological characteristics of the biologic sample. Forexample, if the biologic sample is semen, morphology assay 134 mayanalyze morphological defects of the sperm cells which may degrade itsfertilization potential. Sperm cells morphology assay 134 may bedetached from cartridge 100 and held for further diagnosis.

Reagent locations 136 may each include a reagent container. The reagent,upon contact with the biologic sample, may yield a reaction and/or acolored compound indicating existence and/or concentration of acomponent in the sample. Other reagents such as cell support medium,labeling compounds, markers, peptide and the like, available fromvarious companies, may also be used.

Cell separation system 140 may be adapted to assess motility of spermcells or any other cells of the biologic sample. Additionally oralternatively, cell separation system 140 may be adapted to isolatemotile sperm cells of the semen sample for intra uterine insemination(IUI), vaginal insemination, and/or in-vitro fertilization (IVF)purposes.

Cell separation system 140 may be based upon the principle that motilecells (such as, for example, sperm cells) have swimming abilities,whereas immotile cells lack these abilities, at least to some extent.Therefore, cell separation system 140 is constructed such that motilecells move, essentially using their own swimming capabilities, to adifferent location, while a sediment of immotile cells is left behind.

Reference is now made to FIGS. 3A and 3B, which show cell separationsystem 140 in more detail. FIG. 3A is a cross-sectional view and FIG. 3Bis a top view. Cells separation system 140 may include two chambers: acentral chamber 302 shaped as a dimple in main body 102, and aperipheral chamber 304 shaped as a shallower, circumferential depressionaround the central chamber.

In order to operate cell separation system 140, a biologic sample (suchas semen) 308 is deposited inside central chamber 302, while keeping thesample's level below a rim 306. Rim 306, may be dimensioned and designedwith specific surface roughness or serration in order to facilitaterequired surface tension capabilities for specific sample/reagentcombination. A separation-enabling agent 310, such as a Ringer'ssolution, Hartmann's solution, Saline and/or the like is then introducedinto central chamber 302 and/or into peripheral chamber 304, such thatthe separation-enabling agent covers both the entirety of centralchamber 302 and at least a portion of peripheral chamber 304.

Then, semen sample 308 and separation-enabling agent 310 may be left fora period of optionally 15 to 60 minutes in a temperature of optionally30-37 degrees Celsius, allowing motile cells to swim up throughseparation-enabling agent 310 and at least partially into peripheralchamber 304. After the specified period, the motile cells may becollected, manually or automatically, from peripheral chamber 304.

Cell separation system 140 may also be operated inversely—a sample maybe deposited in peripheral chamber 304 keeping its level below rim 306;a separation-enabling agent may be introduced into central chamber 302while overflowing rim 306 onto the peripheral chamber; and thecomponents may be left to allow motile cells to swim up from theperipheral chamber into the central chamber.

Generally, a cell separation system such as system 140 or any othersystem may be constructed according to the principle that a firstchamber is adapted to contain a semen sample, and a second chamber isadapted to receive motile cells upon introduction of aseparation-enabling agent into the first chamber. In the examples givenabove, respectively, each of central chamber 302 and peripheral chamber304 may be the first or the second chamber.

Cell separation system 140 may be used to assess motility of sperm cellsof the semen sample, and/or to isolate motile sperm cells of the semensample for intra uterine insemination (IUI), vaginal insemination and/orin-vitro fertilization (IVF) purposes.

Referring now back to FIGS. 1A and 1B, free volume compartment 124 maybe adapted to measure and/or to dose the volume or a portion of thevolume of the biologic sample. Free volume compartment 124 may be usedto hold required dose of the sample and than transfer it to the correctassay, as different assays require different volumes of sample. Thevolume may be manually read, such as by reading the scale at the samplesurface level or by a sensor adapted for such reading.

Reference is now made to FIG. 1C, which shows a perspective view ofanother exemplary sealed, removable cartridge 170, according to anembodiment. Cartridge 170 may differ from cartridge 100 (FIGS. 1A-B),inter alia, in its essentially flexible housing 172. Flexible housing172 may be made of any flexible material, such as a polymer, an IVpouch, a food/liquid storage pouch, a hazardous material storage pouch,or any other pouch. Internal conduits 176 may also be flexible, toenable manual or automatic squeezing of housing 172 and the conduits totransport a biologic sample within cartridge 170, towards two or moreassay locations such as assay locations 178 and 180.

An Assay Device

Reference is now made to FIG. 2, which shows an exploded view of anexemplary assay device 200, according to an embodiment. Assay device 200may include a compartment 202 or any other cavity adapted to receive acartridge 204, which may be cartridge 100 of FIGS. 1A-B, cartridge 170of FIG. 1C or any other suitable cartridge. Compartment 202 is shown,for simplicity of presentation, as a space above a base 206 of assaydevice 200. In other embodiments (not shown), a compartment may be aslot, a recess and/or any other cavity adapted for partial or fullinsertion of a cartridge.

Assay device 200 may further include a top cover 208 having a handle210. Top cover 208 may be pivotally connected to base 206, to enableopening of the top cover for insertion and removal of cartridge 204. Inother embodiments (not shown), an assay device may structured such thatinsertion and removal of a cartridge do not necessitate manual openingof a cover, a door or the like. For example, an assay device may includean automatically-opening door or a door which opens upon physicalengagement of a cartridge. Alternatively, an assay device may lack acover or a door at all, so that at least a portion of a cartridgeremains exposed when the cartridge is inside its compartment.

Assay device 200 may further include an actuator 212 adapted tointerface with cartridge 204 and to provide positive and/or negative gas(such as air or any other suitable gas) pressure to the cartridge. Thepressure created by actuator 212 may propagate along one or moreconduits within cartridge 204, so that a biologic sample contained inthe cartridge is transported along the cartridge. Actuator 212 may be apump, such as a positive displacement pump, a peristaltic pump or anyother type of pump adapted to provide positive and/or negative pressureto the one or more conduits of cartridge 204. Additionally oralternatively, a common syringe or a micropipette, manually or machineoperated, may be used.

Additionally or alternatively, a different actuator (not shown) may beat least one roller adapted to squeeze cartridge 204 (or a differentcartridge) in order to transport the biologic sample within it.

Assay device 200 may include a means for reading results, or to inspectany other assay within cartridge 100. Results may be read visually, orthe device may further include one or more sensors, such as, forexample, three sensors 214. At least one of sensors 214 may be adaptedto sense one or more parameters pertaining to the biologic sample incartridge 204, and may be positioned such that it is in sensing stanceof at least one assay location of the cartridge.

For example, at least one of sensors 214 may be an image sensor,namely—a camera, adapted to visually inspect at least one assay locationof cartridge 204. The image sensor may sense, for instance, a color (viasensed wavelength), a texture and/or the like which exist in the atleast one assay ports. The color (via sensed wavelength), a textureand/or shape may be indicative of one or more parameters of the biologicsample. For example, the image sensor may be adapted to sense light at610-670 nanometers (nm) for detecting apoptosis in the biologic sample.As another example, pH may be read by pH electrode; Turbidity andviscosity sensors may be ones available on the market; a pad loaded withspecific reagents also available on the market.

Assay device 200 may further include a processor 216, adapted to controlat least one of sensors 214 and/or to process data received from thesensors. Processor 216 may be realized as any available micro processor,micro controller and/or general purpose computer. For example, processor216 may display locally to its user results of one or more assaysperformed in cartridge 204. The results may be stored for furtherprocessing, displayed in a remote location and/or transferred usingcommunication protocols known in the industry, wired or wireless. Asanother example, if the biologic sample is a semen sample, processor 216may analyze a series of temporally-distinct semen samples of the sameperson, and provide the user with a prediction of an optimal date inwhich the person's semen may be best for fertilization. That is,processor 216 may recognize a pattern of gradually changing fertilityfactors (such as sperm cell concentration, sperm cell motility and/orthe like) and calculate, accordingly, future fertility factors in thatsame tested person. When conducting an assay of female factors, forexample, estrogen and progesterone profiles, it may be possible topredict a date in which fertilization is in its best. Combining bothpredictions yields a better chance for successful fertilization, and an“optimal fertilization date” may be jointly determined.

Processor 216 may be further adapted to perform one or more offacilitating at least one of the assays, receiving a reading from the atleast one sensor, computing a result of at least one of the assays,and/or computing a combined measure of results of two or more of theassays, hence concluding different results. Such a combined measure maybe used as a fertility index. As an example, male subjects with lowsperm qualities may get a higher index score by changing their way oflife, avoiding oxidative stress or other methods known in prior art.

Reference is now made to FIG. 4, which shows a perspective view ofanother assay device 400, according to an embodiment. Assay device 400may be relatively easy to operate and its operation may require nospecial laboratory training, so that a nurse, a physician, or any othercaregiver may operate it in what is often referred to as a “point ofcare”—a clinic, a medical institution or the like. Furthermore, theassay device may still be operated in a laboratory.

Assay device 400 may include a compartment 402 adapted to receive areceptacle, such as a condom or a sample collecting cup, containing areproduction system sample such as semen, vaginal secretions, cervicalmucus, vaginally-collected cells and/or the like. Optionally, thereceptacle is the one disclosed in applicant's PCT Published ApplicationNo. WO 2008/035333.

Referring now to FIG. 4B, an exemplary receptacle 440 is shown.Receptacle 440 may include an elongated, flexible bag, which may have acondom-like shape with inner cavity (such as 443) defined by the wallsof the receptacle bag (440). The narrow end 442A of the receptacle maybe at least partially sealed. For example, the walls at the narrow endof the receptacle may exhibit pore sizes of less then 0.42 nm. The broadend 442B, which is distally opposing the narrow end 442A, may be open.The broad, open end 442B may further include a rim 444 that may be usedfor the association of the receptacle within a contraceptive, asdetailed below herein. Rim 444 is illustrated at a deformed state,wherein the rim is shaped into an eight form, by, for example, pinchingtwo opposing sides of the rim towards each other. The receptacle 440 maybe constructed of rubber, silk, polyurethane, silicone and the like. Thethickness of the receptacle may vary in the range of about 5 to 1500microns. Size of receptacle 140 may vary in length and diameter. Forexample, length of receptacle 440 from end 442A to end 442B may be inthe range of, about 100-200 mm. For example, diameter of rim 444 ofreceptacle 440 may be in the range of, about 37 to 60 millimeter.Receptacle (such as 440) may further be associated with a malecontraceptive device, such as a condom 446. Receptacle 440 may be fittedinto male condom 446, such that the receptacle is contained within theinner space of the condom. Shown in FIG. 4B is a receptacle 440 fittedabout two thirds of its length into a condom 446. Receptacle 440 may besecured to condom 446 by various ways. For example, rim 444 and rim 448of condom 446 may be associated by pressing, stitching, mechanicalfitting, zip-lock fit, zipper fit, fitting grooves, adhering, gluing andthe like. For example, rim 444 of receptacle 440 may includeperforation/grooves that may be used to fit to the upper rim, 448 ofcondom 446.

Reference is now made back to FIG. 4A. Assay device 400 may include anextraction mechanism for extracting the reproduction system sample fromthe receptacle and for transporting the reproduction system sampletowards one or more assay ports and/or treatment ports, where thereproduction system sample is assessed and/or treated, respectively.

The extraction mechanism may be embodied as a strike handle 404pivotally attached to a main body 410 of assay device 400, and having aprotruding structure 406 matching a structure of a recess 408 in themain body. The receptacle may be positioned in compartment 402 with itsreproduction system sample-containing edge at recess 408, and handle 404may be lowered so as to squeeze the receptacle and extract at least someof its reproduction system contents.

Alternatively, the extraction mechanism may include a peristaltic pump(not shown) and/or a set of rollers adapted to induce the reproductionsystem sample out of the receptacle. Alternatively, the extractionmechanism may be the receptacle itself, being elastic in nature andtherefore manually squeezable by a user.

Reference is now made to FIG. 4C, which shows a cross-sectional view ofassay device 400. Before, during or after extraction of the receptacle'sreproduction system contents, the volume of the reproduction system isoptionally measured in a chamber 412.

The extracted reproduction system may be forced, by virtue of theextraction mechanism, to a conduit 414 leading to one or more assaylocations, such as assay location 416. The one or more assays areoptionally those described above in regard to cartridge 100 (FIGS.1A-B).

When the one or more assays are complete, at least one chemical may flowto a result indicator such as a color-changeable result pad 418, causingthe pad to change color responsive to the assay result. Result pad 418may be embedded in a sliding base 420 of assay device, and the slidingbase may be pivotally attached, using a hinge 422, to main body 410.Sliding base 420 may be slid by the user when the one or more assays arecomplete, to reveal result pad 418 and see the result.

Handle 404, or any other part of assay device 400, may include areference color scale (not shown) for comparing the shade, shape,texture and/or the like of result pad 418 to a reference and thusproviding the user with a meaningful result. The reference color scalemay be printed on handle 404 or attached to it as a sticker. Thereference color scale optionally includes literal explanation of themeaning of each color; the explanation may, additionally oralternatively, be included in product literature accompanying assaydevice 400.

Optionally, assay location 416 is a replaceable, and is adapted to bereplaced by an additional assay location for facilitating an additionalassay. This way, assay device 400 may be used multiple types forperforming the same assay (such as an assay pertaining to fertilizationpotential which may have to be repeated every once in a while) or may beused each time for performing a different assay of the same semen sampleor a different semen sample.

While a number of exemplary aspects and embodiments have been discussedabove, those of skill in the art will recognize certain modifications,permutations, additions and sub-combinations thereof. It is thereforeintended that the following appended claims and claims hereafterintroduced be interpreted to include all such modifications,permutations, additions and sub-combinations as are within their truespirit and scope.

In the description and claims of the application, each of the words“comprise” “include” and “have”, and forms thereof, are not necessarilylimited to members in a list with which the words may be associated.

1-28. (canceled)
 29. A cell separation system, wherein said systemcomprising: a. a first chamber adapted to contain at least a portion ofa cell sample; at least a portion of said sample is characterized by atleast one biological or chemical characteristic; said first chamber isbounded by a rim, such that said cell sample is kept below said rim;and, b. a second peripheral chamber; said second peripheral chamber ischaracterized by a circumferential depression around said first chamber;said second chamber is adapted to enable isolation of said at least aportion of said cell sample having the same biological or chemicalcharacteristic, upon introduction of a separation-enabling agent. 30.The cell separation system according to claim 29, wherein said cellseparation system is used for separating sperm cells from a semensample; further wherein said same biological or chemical characteristicis motility of said sperm cells.
 31. cell separation system according toclaim 30, further adapted to assess concentration motile of sperm cellsand/or isolate motile sperm cells within a semen sample for assistingfertility.
 32. The cell separation system according to claim 30, whereinsaid rim is configured with specific surface roughness or serration tofacilitate required surface tension capabilities for specificsample/reagent combination.
 33. The cell separation system according toclaim 30, wherein said separation-enabling agent is selected from agroup consisting of Ringer's solution, Hartmann's solution, Saline,adapted to facilitate said separation of said semen sample or any cellsupport medium, cell washing medium, preparation medium or cellseparation enabling agent.
 34. The cell separation system according toclaim 29, additionally comprising a reagent selected from a groupconsisting of selected from a group consisting of cell support medium,labeling compounds, markers, peptide, color-changeable pad; said reagentis adapted to, upon contact with said biologic sample, to yield areaction and/or a colored compound indicating (i) existence or (ii)concentration of a component in said sample (iii) a result of said atleast one assay.
 35. The cell separation system according to claim 29,wherein said sample is selected from a group consisting of: a semensample, a vaginal secretion sample, a vaginal cell sample, a bloodsample, a urine sample, a saliva sample, a lymph sample or anycombination thereof.
 36. The cell separation system according to claim29, adapted to enable an assay; further wherein said assay is selectedfrom a group consisting of: a sperm concentration assay, a semen pHassay, a leukocyte threshold assay, a sperm motility assay, a spermmorphology assay, a semen volume assay, a viscosity assay and aturbidity assay; further wherein said assays is adapted to facilitatediagnosis of at least one sexually transmitted disease (STD) selectedfrom a group consisting of: syphilis, gonorrhea, Candida, human papilomavirus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV),Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas and HepatitisC.
 37. The cell separation system according to claim 30, further adaptedto isolate motile sperm of said semen sample for a usage selected from agroup consisting of: intra uterine insemination (IUI), vaginalinsemination, and in-vitro fertilization (IVF) and diagnosis of motilesperm cell.
 38. The cell system according to claim 30, enclosed within acartridge adapted for insertion into an assay device.
 39. The cellsystem according to claim 38, wherein said cartridge comprising a body;said body comprises: (i) at least one compartment adapted to containsaid at least one biologic sample; and, (ii) at least one assaylocation, in which said assay of said at least one biologic sample isenabled; b. at least one actuator adapted to interface with saidcartridge to enable transportation of said biologic sample to at leastone of said assay locations.
 40. The cell system according to claim 39,additionally comprising a reagent selected from a group consisting ofcell support medium, labeling compounds, markers, peptide,color-changeable pad; said reagent is adapted to, upon contact with saidbiologic sample, to yield a reaction and/or a colored compoundindicating (i) existence or (ii) concentration of a component in saidsample (iii) a result of said at least one assay.
 41. The cell systemaccording to claim 40, wherein said biologic sample is selected fromgroup consisting of: a semen sample, a vaginal secretion sample, avaginal cell sample, a blood sample, a urine sample, a saliva sample anda lymph sample or any combination thereof; further wherein said assay isselected from a group consisting of: a sperm concentration assay, asemen pH assay, a leukocyte threshold assay, a sperm motility assay, asperm morphology assay, motile sperm cell concentration, a semen volumeassay, a viscosity assay and a turbidity assay.
 42. The cell systemaccording to claim 40, wherein said assay is adapted to facilitatediagnosis of at least one sexually transmitted disease (STD) selectedfrom a group consisting of: syphilis, gonorrhea, Candida, human papilomavirus (HPV), mycoplasma, ureaplasma, human immunodeficiency virus (HIV),Chlamydia, herpes simplex virus, Hepatitis B, Trichomonas and HepatitisC.
 43. The cell system according to claim 40, wherein said cartridge ismade of substantially rigid materials or substantially flexiblematerials or any combination thereof.
 44. The cell system according toclaim 40, wherein said actuator comprises a pump, a peristaltic pump,means of pressure difference creation, strike handle, a set of rollers,manual activation selected from a pipette, micropipette injector,syringe, any positive displacement or any combination thereof.
 45. Thecell system according to claim 40, further comprising a control meansadapted to (i) receive a reading from at least one sensor, said sensoris in communication with said cartridge; (ii) analyze said reading;(iii) analysis readings received based upon said at least one of saidassays; and (iv) output said analysis of said biological sample.
 46. Amethod for separating cells from a biological sample, said methodcomprising steps of: a. providing a cell separation system comprising: afirst chamber; said first chamber is bounded by a rim; and a secondperipheral chamber shallower, circumferential depression around saidfirst chamber; b. depositing at least a portion of said biologicalsample into said first chamber of said cell separation system such thatsaid cell sample is kept below said rim; at least a portion of saidsample is characterized by at least one biological or chemicalcharacteristic; c. introducing a separation-enabling agent into eithersaid first chamber or said second chamber; thereby facilitating movementof said at a portion of said cell sample having the same biological orchemical characteristic into said second chamber of said cell separationsystem.
 47. The method according to claim 46, additionally comprising atleast one step selected from (i) collecting said motile cells for ausage selected from a group consisting of: IUI, vaginal insemination,and IVF and diagnosis of motile sperm cell; or (ii) assessing motilityof said sperm cells based on a relative amount of motile cells in saidsecond chamber.
 48. The method according to claim 46, additionallycomprising step of selecting said separation-enabling agent from a groupconsisting of Ringer's solution, Hartmann's solution, Saline, adapted tofacilitate said separation of said semen sample, or any cell supportmedium, cell washing medium, preparation medium or cell separationenabling agent.
 49. The method according to claim 48, additionallycomprising at least one step selected from (a) providing a reagentadapted to, upon contact with said biologic sample, to yield a reactionand/or a colored compound indicating (i) existence or (ii) concentrationof a component in said sample (iii) a result of said at least one assay;or (b) selecting said reagent from a group consisting of cell supportmedium, labeling compounds, markers, peptide, color-changeable pad orany combination thereof.
 50. The method according to claim 46,additionally comprising step of selecting said sample from a groupconsisting of: a semen sample, a vaginal secretion sample, a vaginalcell sample, a blood sample, a urine sample, a saliva sample, a lymphsample or any combination thereof.
 51. The method according to claim 46,additionally comprising at least one step selected from (a) performingan assay; further wherein said assay is selected from a group consistingof: a sperm concentration assay, a semen pH assay, a leukocyte thresholdassay, a sperm motility assay, a sperm morphology assay, motile spermconcentration assay, a semen volume assay, a viscosity assay and aturbidity assay; or, (b) facilitating diagnosis of at least one sexuallytransmitted disease (STD) selected from a group consisting of: syphilis,gonorrhea, Candida, human papiloma virus (HPV), mycoplasma, ureaplasma,human immunodeficiency virus (HIV), Chlamydia, herpes simplex virus,Hepatitis B, Trichomonas and Hepatitis C.